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WHIPPANY, N.J.--( BUSINESS WIRE )--Bayer today announced the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for the oral androgen receptor inhibitor (ARi) NUBEQA ® (darolutamide) in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). “ Simply put, our ambition is to help more patients with prostate cancer,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer. “ We are proud of the role NUBEQA currently plays in the treatment of mHSPC and with this FDA submission, hope to expand the use of NUBEQA to more patients with the disease, regardless of chemotherapy use.” The submission is based on positive results from the investigational pivotal Phase III ARANOTE trial. Data from the trial were presented at the 2024 European Society for Medical Oncology (ESMO) Congress and published in The Journal of Clinical Oncology . NUBEQA is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. About the ARANOTE Trial 1 The ARANOTE trial (NCT04736199) was a randomized, double-blind, placebo-controlled Phase III study designed to assess the efficacy and safety of NUBEQA plus androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). 669 patients were randomized to receive 600mg of NUBEQA twice daily or matching placebo in addition to ADT. The primary endpoint of this study was radiological progression-free survival (rPFS), measured as time from the date of randomization to the date of first documentation of radiological disease progression or death due to any cause, whichever occurs first. Secondary endpoints included overall survival (time from randomization to the date of death from any cause), time from randomization to the date of first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety assessments. About NUBEQA ® (darolutamide) 2 NUBEQA ® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. In addition to the ARANOTE trial, NUBEQA is being evaluated in a robust clinical development program, which includes studies across various stages of prostate cancer, including in the ARASTEP Phase III trial evaluating NUBEQA plus ADT versus ADT alone in HSPC patients with high-risk biochemical recurrence (BCR) and no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline, as well as in the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating NUBEQA as an adjuvant treatment for localized prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov. INDICATIONS NUBEQA ® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of adult patients with: Non-metastatic castration-resistant prostate cancer (nmCRPC) Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel IMPORTANT SAFETY INFORMATION Warnings & Precautions Ischemic Heart Disease – In a study of patients with nmCRPC (ARAMIS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA versus 2.5% receiving placebo, including Grade 3-4 events in 1.7% vs. 0.4%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA vs. 0.2% receiving placebo. In a study of patients with mHSPC (ARASENS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel vs. 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel vs. 0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease. Seizure – In ARAMIS, Grade 1-2 seizure occurred in 0.2% of patients receiving NUBEQA vs. 0.2% receiving placebo. Seizure occurred 261 and 456 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.6% of patients receiving NUBEQA with docetaxel, including one Grade 3 event, vs. 0.2% receiving placebo with docetaxel. Seizure occurred 38 to 340 days after initiation of NUBEQA. It is unknown whether antiepileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment. Embryo-Fetal Toxicity – Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose. Adverse Reactions In ARAMIS, serious adverse reactions occurred in 25% of patients receiving NUBEQA vs. 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA vs. 3.2% of patients receiving placebo. Fatal adverse reactions in patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common adverse reactions (>2% with a ≥2% increase over placebo), including laboratory test abnormalities, were increased AST, decreased neutrophil count, fatigue, increased bilirubin, pain in extremity and rash. Clinically relevant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease and heart failure. In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel vs. 42% of patients receiving placebo with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), decreased neutrophil count (2.8%), musculoskeletal pain (2.6%), and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel vs. 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with docetaxel) were constipation, rash, decreased appetite, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia. Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures, ischemic heart disease, seizures, and drug-induced liver injury. Drug Interactions Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use. Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed. Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate. NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates. Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA. For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information . About Metastatic Hormone-Sensitive Prostate Cancer Prostate cancer is the second most common cancer in men and the fifth most common cause of cancer death in men worldwide. 3 In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, including almost 300,000 cases in the U.S., and about 375,000 died from the disease worldwide. 4,5 At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately 10% of men will already present with mHSPC when first diagnosed. 6,7,8 Men with metastatic hormone-sensitive prostate cancer (mHSPC) will start their treatment with hormone therapy, such as ADT, androgen receptor inhibitor (ARi) plus ADT or a combination of the chemotherapy docetaxel and ADT. Despite this treatment, most men with mHSPC will eventually progress to castration-resistant prostate cancer (CRPC), a condition with limited survival. About Oncology at Bayer Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.com . © 2024 Bayer BAYER, the Bayer Cross and NUBEQA are registered trademarks of Bayer. Find more information at www.pharma.bayer.com Our online press service is just a click away: www.bayer.us/en/newsroom Follow us on Facebook: http://www.facebook.com/pharma.bayer Follow us on X: https://X.com/BayerUS Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References NUBEQA (darolutamide) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; October 2023. Journal of Clinical Oncology (ascopubs.org). Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial . https://ascopubs.org/doi/10.1200/JCO-24-01798 . September 2024. Hyuna S et al. Ca Cancer J Clin 2021 ; 71:209–249. Prostate Cancer: Statistic. Cancer.Net. https://www.cancer.net/cancer-types/prostate-cancer/statistics . September 2024. American Cancer Society. Cancer Facts & Figures 2024. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2024-cancer-facts-figures.html . September 2024. Piombino C et al. Cancers (Basel). 2023 Oct 11;15(20):4945. Helgstrand JT et al. Cancer. 2018;124(14):2931-2938. Buzzoni C et al. Eur. Urol. 2015;68:885–890. PP-NUB-US-3569-1 9/24

Abstract: LBA68 WHIPPANY, NJ, USA I September 16, 2024 I Results from the investigational pivotal Phase III ARANOTE trial demonstrated that NUBEQA ® (darolutamide) plus androgen deprivation therapy (ADT) showed a statistically significant and clinically meaningful improvement in radiological progression-free survival (rPFS) compared to placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC). 1 The results were presented today as a late-breaking oral presentation at the 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain and published simultaneously in The Journal of Clinical Oncology . The results were consistent with the established safety profile of NUBEQA, with no new safety signals observed. Rates of serious adverse events were similar between the treatment arms (23.6% for NUBEQA plus ADT compared to 23.5% for placebo plus ADT), while discontinuation due to treatment-emergent adverse events (TEAEs) was 6.1% in patients treated with NUBEQA plus ADT compared to 9% in patients receiving placebo plus ADT. 1 NUBEQA is indicated in the U.S. for the treatment of adult patients with mHSPC in combination with docetaxel and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC). 2 The randomized, double-blind, placebo-controlled Phase III ARANOTE trial was designed to assess the efficacy and safety of NUBEQA plus ADT in patients with mHSPC. A total of 669 patients were randomized 2:1 to receive either 600 mg of NUBEQA (N=446) or placebo (N=223) twice daily in addition to ADT. 1 “Each diagnosis of metastatic hormone-sensitive prostate cancer is unique, shaped by factors such as age, comorbidities and patient preferences. Each patient therefore requires a tailored treatment approach that thoughtfully addresses these key considerations,” said Fred Saad, Professor and Chairman of Surgery and Director of Genitourinary Oncology at the University of Montreal Hospital Center (CHUM), and Principal Investigator of the ARANOTE trial. “With the positive results from ARANOTE, in addition to the ARASENS data, darolutamide has now demonstrated efficacy and safety data both with and without chemotherapy in mHSPC.” “The positive outcomes from the ARANOTE trial provide physicians with additional data that could broaden the use of NUBEQA as a treatment option for more patients with metastatic hormone-sensitive prostate cancer, which accounts for approximately 10% of prostate cancer diagnoses in the United States,” said Neal Shore, M.D., FACS, Medical Director, Carolina Urologic Research Center. “These data demonstrate the potential of this therapy to provide significant benefits to patients with mHSPC, regardless of chemotherapy use.” “The ARANOTE trial was designed to investigate NUBEQA plus ADT compared to placebo plus ADT to provide an additional treatment option for patients with metastatic hormone-sensitive prostate cancer,” said Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division. “Supported by our robust clinical development program, our goal is to expand the option of NUBEQA to as many patients as possible.” Bayer plans to submit the data from the ARANOTE trial to the U.S. Food and Drug Administration (FDA) to support the expanded use of NUBEQA in patients with mHSPC. Detailed Results from ARANOTE 1 Results of the rPFS analysis were consistent across prespecified subgroups, including 40% risk reduction (HR 0.60, 95% CI: 0.44-0.80) in patients with high-volume mHSPC and 70% risk reduction (HR 0.30, 95% CI: 0.15-0.60) in patients with low-volume disease. An analysis of immature overall survival data (OS), which measures the time from treatment until death from any cause, showed an HR of 0.81 (95% CI 0.59-1.12) versus placebo plus ADT. The ARANOTE data also suggested clinical benefits across all other secondary endpoints, including delaying the time to castration-resistant prostate cancer (CRPC) (HR 0.40; 95% CI, 0.32-0.51), time to PSA progression (HR 0.31; 95% CI 0.23-0.41), time to pain progression (HR 0.72; 95% CI 0.54-0.96), and time to initiation of subsequent systemic therapy (HR 0.40; 95% CI 0.29-0.56), compared to placebo plus ADT, though not assessed for statistical significance. Incidence rates for adverse events Grade 3 or higher were similar between the two groups (35.5% and 35.7%, respectively). The incidence of fatigue was lower with NUBEQA plus ADT than with placebo plus ADT (5.6% and 8.1%, respectively). About the ARANOTE Trial 1 The primary endpoint of the ARANOTE trial is rPFS, measured as time from randomization to date of first documented radiological disease progression or death due to any cause, whichever occurs first. Secondary endpoints include overall survival (time to death from any cause), time to first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety assessments. About the ARASENS Trial 3 The ARASENS trial (NCT02799602) is the only randomized Phase III, multi-center, double-blind, placebo-controlled trial prospectively designed to compare the use of a second-generation androgen receptor inhibitor (ARi) (NUBEQA) plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel to ADT plus docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of NUBEQA twice a day or matching placebo plus ADT and docetaxel. The primary endpoint of the trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), and time to initiation of subsequent anticancer therapy, all measured at 12-week intervals, as well as adverse events (AEs) as a measure of safety and tolerability. About NUBEQA ® (darolutamide) 2 NUBEQA ® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. In addition to the ARANOTE trial, darolutamide is being evaluated in a robust clinical development program, which includes studies across various stages of prostate cancer, including in the ARASTEP Phase III trial evaluating darolutamide plus ADT versus ADT alone in HSPC patients with high-risk biochemical recurrence (BCR), no evidence of metastatic disease by conventional imaging, and a positive PSMA PET/CT at baseline, as well as in the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating NUBEQA as an adjuvant treatment for localized prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov. NUBEQA is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. INDICATIONS NUBEQA ® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of adult patients with: For important risk and use information about NUBEQA, please see the full Prescribing Information . About Metastatic Hormone-Sensitive Prostate Cancer Prostate cancer is the second most common cancer in men and the fifth most common cause of cancer death in men worldwide. 4 In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, including almost 300,000 cases in the U.S., and about 375,000 died from the disease worldwide. 5,6 At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately 10% of men will already present with mHSPC when first diagnosed. 7,8,9 Men with metastatic hormone-sensitive prostate cancer (mHSPC) will start their treatment with hormone therapy, such as ADT, androgen receptor inhibitor (ARi) plus ADT, or a combination of the chemotherapy docetaxel and ADT. Despite this treatment, most men with mHSPC will eventually progress to castration-resistant prostate cancer (CRPC), a condition with limited survival. About Oncology at Bayer Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.com . © 2024 Bayer BAYER, the Bayer Cross and NUBEQA are registered trademarks of Bayer. Find more information at www.pharma.bayer.com Our online press service is just a click away: www.bayer.us/en/newsroom Follow us on Facebook: http://www.facebook.com/pharma.bayer Follow us on X: https://x.com/BayerUS References SOURCE: Bayer

ORION CORPORATION PRESS RELEASE 16 SEPTEMBER 2024 at 11.30 EEST Darolutamide plus androgen deprivation therapy significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer Results from the pivotal Phase III ARANOTE trial evaluating darolutamide plus androgen deprivation therapy (ADT) showed a statistically significant increase in radiological progression-free survival (rPFS) compared to placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer Darolutamide plus ADT now has positive data both with and without docetaxel based on two pivotal Phase III studies in metastatic hormone-sensitive prostate cancer Safety analysis reconfirms the established tolerability profile of darolutamide as observed in the ARAMIS and ARASENS trialsData from ARANOTE trial presented as a late-breaking oral presentation at the ESMO 2024 Congress and simultaneously published in The Journal of Clinical Oncology Abstract: LBA68 Results from the Phase III ARANOTE trial have shown that darolutamide plus androgen deprivation therapy (ADT) significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT (HR 0.54; 95% CI 0.41–0.71; P<0.0001), in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Consistent benefits in rPFS were observed across prespecified subgroups, including patients with high- and low-volume mHSPC. Treatment emergent adverse event (TEAEs) were low and similar between treatment groups. The results were presented at the 2024 ESMO Congress and have been simultaneously published in The Journal of Clinical Oncology. “Darolutamide, a compound originated by Orion R&D, continues to deliver clinical benefit in patients with metastatic hormone-sensitive prostate cancer, now in ARANOTE with ADT alone and earlier in ARASENS in combination with ADT and docetaxel. These results also reflect our fruitful collaboration with Bayer for more than ten years with a focus to deliver new personalised treatment options to the patients with prostate cancer,” said Professor, M.D., Ph.D. Outi Vaarala, Senior Vice President of Innovative Medicines and Research & Development at Orion. Bayer plans to submit the data from the ARANOTE trial to health authorities globally to support the expanded use of darolutamide in patients with mHSPC. Darolutamide is already approved for the treatment of patients with mHSPC under the brand name Nubeqa® in combination with ADT and docetaxel in more than 80 markets, and for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease, in over 85 countries around the world. The product is developed jointly by Orion and Bayer. Detailed results from ARANOTEDarolutamide plus ADT significantly reduced the risk of radiological progression or death by 46% (HR 0.54; 95% CI 0.41–0.71; P<0.0001), compared with placebo plus ADT. Consistent benefits in rPFS were observed across patient subgroups, including high- and low-volume mHSPC, with a risk reduction by 40% and 70% (HR 0.60; 95% CI 0.44-0.80 and HR 0.30; 95% CI 0.15-0.50) respectively. An analysis of immature data of overall survival (OS), which measures the time from treatment until death from any cause, was suggestive of a potential benefit with darolutamide plus ADT (HR=0.81, 95% CI 0.59-1.12) vs placebo plus ADT. The ARANOTE data also suggested numerical clinical benefits across all other secondary endpoints including delaying the time to CRPC (HR 0.40; 95% CI, 0.32–0.51), time to PSA progression (HR 0.31; 95% CI 0.23–0.41), time to pain progression (HR 0.72; 95% CI, 0.54–0.96), and time to initiation of subsequent systemic therapy (HR 0.40; 95% CI, 0.29–0.56), compared to placebo plus ADT. Incidences of treatment-emergent adverse events (TEAEs) were low (most were grade 1 or 2) and similar between treatment arms, and treatment discontinuations due to TEAEs were lower in patients receiving darolutamide compared to placebo plus ADT (6.1% vs 9.0%). The most frequently reported AEs (incidence of ≥10%) for darolutamide plus ADT vs placebo, were anemia (20.4% and 17.6%, respectively), arthralgia (12.4% and 11.3%, respectively), and urinary tract infections (11.7% and 7.7%, respectively). The incidence of fatigue was lower with darolutamide plus ADT vs placebo (5.6% and 8.1%, respectively). Incidence of TEAEs of interest were minimal between treatment arms, with a difference of ≤2% for coronary artery disorders, cardiac arrhythmias, and vasodilation/flushing. About the ARANOTE TrialThe ARANOTE trial is a randomized, double-blind, placebo-controlled Phase III study designed to assess the efficacy and safety of darolutamide plus ADT in patients with mHSPC. 669 patients were randomized 2:1 to receive either 600mg of darolutamide twice daily or placebo in addition to ADT. The primary endpoint of this study is rPFS, measured as time from randomization to date of first documented radiological progressive disease or death due to any cause, whichever occurs first. Secondary endpoints include overall survival (time to death from any cause), time to first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety assessments. About darolutamideDarolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the androgen receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. This is also supported by the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial and the maintained verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial. ARANOTE is part of a robust clinical development program investigating darolutamide across various stages of prostate cancer, which includes the Phase III ARASTEP trial evaluating darolutamide plus ADT compared to ADT alone in hormone-sensitive high-risk biochemical recurrence (BCR) prostate cancer, who have no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT scan at baseline. Furthermore, darolutamide is also being investigated by Bayer in the collaborative Phase III DASL-HiCaP (ANZUP1801) trial led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). The study evaluates darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence. About Metastatic Hormone-Sensitive Prostate CancerProstate cancer is the second most common cancer in men and the fifth most common cause of cancer death in men worldwide.1 In 2022, an estimated 1.5 million men were diagnosed with prostate cancer, and about 397,000 died from the disease worldwide.1 Prostate cancer diagnoses are projected to increase from 1.4 million annually in 2020 to 2.9 million by 2040.2 At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. mHSPC is a stage in the disease where the cancer has spread outside of the prostate to other parts of the body. Up to 10% of men will present with mHSPC when first diagnosed.3,4,5 For patients with mHSPC, ADT is the cornerstone of treatment, often in combination with chemotherapy docetaxel and/or an androgen receptor inhibitor (ARi). Despite treatment, most men with mHSPC will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival. Contact person:Outi Vaarala, SVP, Innovative Medicines and Research & Development, Orion CorporationTel. +358 10 426 3472 References Bray F et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21834 Accessed: August 2024. James ND et al. Lancet 2024; 403: 1683–722.Piombino C et al. Cancers (Basel). 2023 Oct 11;15(20):4945.Helgstrand JT et al. Cancer. 2018;124(14):2931-2938.Buzzoni C et al. Eur. Urol. 2015;68:885–890. Publisher:Orion CorporationCommunicationsOrionintie 1A, FI-02200 Espoo, Finlandhttp://www.orion.fi/en http://www.twitter.com/OrionCorpIR Orion is a globally operating Finnish pharmaceutical company – a builder of well-being for over a hundred years. We develop, manufacture and market human and veterinary pharmaceuticals and active pharmaceutical ingredients. Orion has an extensive portfolio of proprietary and generic medicines and consumer health products. The core therapy areas of our pharmaceutical R&D are oncology and pain. Proprietary products developed by Orion are used to treat cancer, neurological diseases and respiratory diseases, among others. Orion's net sales in 2023 amounted to EUR 1,190 million and the company had about 3,600 employees at the end of the year. Orion's A and B shares are listed on Nasdaq Helsinki.